Mitochondrial genetic landscape and its correlation with immune cell infiltration in preeclampsia: Insights from bioinformatics

Abstract

Background

Preeclampsia (PE), a hypertensive pregnancy disorder, remains a leading cause of maternal and perinatal morbidity and mortality. Mitochondria-related placental metabolic dysfunction is implicated in PE, but its mechanistic role is unclear. This study aimed to identify mitochondria-related genes (MRGs) and their possible regulatory mechanisms in PE.

Methods

Differentially expressed mitochondria-related genes (MRGs) of PE were identified from Gene Expression Omnibus (GEO) dataset GSE114691 and GSE190971. LASSO regression analysis was used to screen key MRGs. Datasets GSE75010 and GSE25906 were used to validate the efficiency of the MRGs predictive model via receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was conducted to verify underlying biological pathways in PE. Furthermore, we investigated the correlation analysis of MRGs and immune cell infiltration, as well as the association between the MRGs and clinical features. Single-cell sequencing analysis and immunofluorescence staining were used to verify the expression of critical gene in the placenta.

Results

Five hub MRGs (MOCS1, CYP11A1, GATM, SFXN3, and BCL2L11) showed high diagnostic accuracy for PE and correlated with immune cell infiltration. CYP11A1 was further associated with Hemolysis, Elevated Liver enzymes, Low platelets (HELLP) syndrome and predominantly expressed in extravillous trophoblasts, with upregulated expression in PE placenta.

Conclusion

The interaction between MRGs with the immune microenvironment might be vital in the development of PE. Among 5 hub MRGs, CYP11A1 might be a potential biomarker of HELLP syndrome. These findings provide novel insights into the underlying pathophysiology of PE and the discovery of new therapeutic targets.